{
 "cells": [
  {
   "cell_type": "code",
   "execution_count": 1,
   "metadata": {},
   "outputs": [
    {
     "name": "stderr",
     "output_type": "stream",
     "text": [
      "Using TensorFlow backend.\n"
     ]
    }
   ],
   "source": [
    "import numpy as np\n",
    "from sklearn.model_selection import ShuffleSplit\n",
    "from data_utils import ENTITIES, Documents, Dataset, SentenceExtractor, make_predictions\n",
    "from data_utils import Evaluator\n",
    "from models import build_lstm_crf_model\n",
    "from gensim.models import Word2Vec"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## read data"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 2,
   "metadata": {},
   "outputs": [],
   "source": [
    "data_dir = '/workspace/data/tianchi_ruijin/ruijin_round1_train2_20181022/'\n",
    "ent2idx = dict(zip(ENTITIES, range(1, len(ENTITIES) + 1)))\n",
    "idx2ent = dict([(v, k) for k, v in ent2idx.items()])"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 3,
   "metadata": {},
   "outputs": [],
   "source": [
    "docs = Documents(data_dir=data_dir)\n",
    "rs = ShuffleSplit(n_splits=1, test_size=20, random_state=2018)\n",
    "train_doc_ids, test_doc_ids = next(rs.split(docs))\n",
    "train_docs, test_docs = docs[train_doc_ids], docs[test_doc_ids]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 4,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div class=\"entities\" style=\"line-height: 2.5\">基础研究</br>基金项 目: 2013 年 河 南 省 基 础 与 前 沿 技 术 研 究 计 划 项 目</br>(132300410111)</br><mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>在高糖环境下对 MC3T3-E1 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖、分化和</br>凋亡的影响</br>张娟  张会娟  靳爽  张维  周浩峰</br>[提要]   以 1、10、20 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>处理 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">48 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 后,利用 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">CCK-8 比色法<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>检测细胞的增</br>殖率,<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">流式细胞术<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>检测凋亡率,实时荧光定量 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 检测<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">I型胶原蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨桥蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>)的表达。</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Western 印迹法<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>检测凋亡相关蛋白 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达。 结果显示与对照组相比,随着<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>浓度的升高,</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">增殖率<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark><mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">逐渐上升<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>(P<0. 05),<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">凋亡率<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark><mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">逐渐下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>(P<0. 05),<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>、<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN mRNA<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 和 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2 蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark></br>表达<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">逐步升高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>(均 P<0. 05),<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax 蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的表达<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">逐步下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>(P<0. 05)。 提示<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>能够在<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">高糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>环境下促进</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖和分化,并抑制其凋亡,且在一定范围内具有浓度依赖性。</br>[关键词]   <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>; MC3T3-E1 成骨细胞; 增殖; 分化; 凋亡</br>Effect of glyburide on the proliferation,differentiation, and apoptosis of MC3T3-E1 osteoblasts under high</br>glucose Zhang Juan, Zhang Huijuan, Jin Shuang, Zhang Wei, Zhou Haofeng. Department of Endocrinology, the</br>First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China</br>[Summary]   After MC3T3-E1 cells were treated with 1, 10, and 20 μmol / L glibenclamide for 48 h, the</br>proliferation rate of cells was detected by CCK-8 assay. Flow cytometry was used to test cell apoptosis. The mRNA</br>expressions of collagen I (<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>) and osteopontin (<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>) were tested by realtime fluorescence quantitative PCR.</br>Western blot was used to detect the expression levels of apoptosis-related proteins <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> and Bcl-2. The results showed</br>that compared with the control group, the proliferation rate of MC3T3-E1 cells was gradually increased(P<0. 05), the</br>apoptosis rate decreased ( P < 0. 05), the expressions of <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA, <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> mRNA, and <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> protein were</br>progressively raised (P<0. 05), and the expression of <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> protein were gradually decreased (P<0. 05) along with</br>increasing concentration of glyburide. It suggested that glibenclamide could promote the proliferation and</br>differentiation of MC3T3-E1 cells in high glucose and may inhibit apoptosis in a concentration-dependent manner</br>within a certain range.</br>[Key words]  Glyburide; MC3T3-E1 osteoblasts; Proliferation; Differentiation; Apoptosis</br>(Chin J Endocrinol Metab, 2015, 31: 462-464)</br>近年来<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>已被认为是<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的慢性并发症之一[1] 。</br>多项大型临床研究发现,应用不同<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">降糖药物<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>的患者<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的发生</br>率有显著差异,其中应用<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">噻唑烷二酮类<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>药物者<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的发生率最</br>高,<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">胰岛素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>次之,再其次为<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">二甲双胍<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>,<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>发生率最低的是应用</br><mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">磺脲类降糖药<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>的患者[2,3] 。 基础研究已证实,<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">噻唑烷二酮类<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>药</br>物激活 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PPARγ<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨髓间充质干细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>成骨分化,<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">促使其成脂分化<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>[4,5] 。 <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">二甲双胍<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>能促进<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖、分化和矿化,抑</br>制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">破骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的分化,促使<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨髓间充质干细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>成骨分化,抑制其</br>成脂分化,对骨代谢起保护作用[6,7] 。 关于<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">磺脲类药物<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨组织<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的直接影响,国外尚未见相关报道,而国内仅见马攀等[8,9] 报</br>道<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列美脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>可以促进大鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">下颌骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的葡萄糖摄取,通过</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">磷脂酰肌醇 3 激酶 /蛋白激酶 B 通路<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>直接促进大鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的</br>增殖和分化。 <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>作为第二代<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">磺脲类降糖药<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>,临床应用广</br>泛,且在国外常用于<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>合并妊娠的患者。 <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>是否也</br>同<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列美脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>一样能够直接作用于<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>并对其增殖、分化和</br>凋亡产生影响,本实验拟通过体外培养的 MC3T3-E1 成骨细胞</br>进行探讨。</br>一、 材料和方法</br>1. 材料:MC3T3-E1 细胞(上海生命科学研究院细胞资源</br>中心),<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark> (德国 Ruibio 公司),α-MEM 培养基 (美国</br>Gibco 公司),胎牛血清(美国 Hycolon 公司),细胞计数试剂盒</br>(CCK-8,上海贝博生物公司),Annexin-FITC /碘化丙啶(PI)双</br>染试剂盒(南京凯基生物科技发展有限公司),超纯 RNA 提取</br>试剂盒(北京康为世纪公司),逆转录试剂盒、cDNA 第一链合</br>成试剂盒(日本 TOYOBO 公司),I型胶原蛋白(<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)引物、</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨桥蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>)引物(上海生物工程有限公司),<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 抗体、</br>Bcl-xl 抗体、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 抗体(Cell signaling technology 公司)。</br>2. 方法:(1)细胞培养:配制含 10% 胎牛血清、1% <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">青链霉素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>双抗的 α-MEM 培养基(葡萄糖浓度为 16. 5 mmol / L)组成的</br>完全培养基。 将 MC3T3-E1 细胞置于 5% 二氧化碳、37℃ 的</br>培养箱中培养。 (2)<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">CCK-8 比色法<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>检测细胞增殖率:将密度</br>为 1×10 4个 / ml 的细胞接种于 96 孔板上, 次日加 0、1、10 和</br>20 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>培养 48 h,并设空白组(未加药物和细胞)。</br>弃去旧培养液,加入配置好的含 CCK-8 的培养液 100 滋l,孵育 2</br>h,于 450 nm 波长处测定各孔吸光度(A 值)。 (3)<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">流式细胞术<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark></br>检测细胞凋亡率:将密度为 1×105 / ml 的细胞接种于 6 孔板上,</br>次日加 0、1、10 和 20 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>培养 48 h。 将细胞消化</br>后,每组取细胞悬液 5 ml 置于流式管中,每管依次加入 5 滋l</br>Annexin V-FITC 和 5 滋l PI,避光反应 15 min。 加入 300 滋l 的结</br>合缓冲液,立即用<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">流式细胞仪<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>检测。 (4)实时荧光定量 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 检</br>测 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的表达:将密度为 1×105 / ml 的细胞接种于 25</br>cm3培养瓶中,处理条件同上,按照 Trizol 试剂说明书提取总</br>RNA。 测定 RNA 纯度和含量。 然后按照试剂说明书进行逆转</br>录反应,引物序列:<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 上游引物为 5'-GTGGCGGTTATGACT-</br>TCAGC-3',下游引物为 5'-TCACGAACAACGTTAG-CATC3忆;<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark></br>上游引物为 5'-GTGGCGGTTATGAC-TTCAGC-3',下游引物为 5'-</br>TCACGAACCACGTTAGCATC-3';β-actin 上游引物为 5'-GTCTCC-</br>TCACCCTCCCAAAAG-3',下游引物为 5'-GCTGCCTCAACACCTC-</br>AACCC-3'。 避光配制 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 反应体系,置于荧光定量 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 仪内</br>进行反应。 应用 MXpro 软件进行数据分析,采用 2-△△Ct法计算</br>目的基因表达的相对变化。 (5)<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Western 印迹法<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>检测 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>的表达:将 MC3T3-E1 细胞以 1×105 / ml 接种于 6 孔板上,按上</br>述条件孵育 48 h。 弃去培养液,裂解细胞,提取蛋白,经 SDS-聚</br>丙烯酰胺凝胶电泳后,将蛋白转移至 PVDF 膜上,脱脂奶粉封</br>闭 1 h,然后将 PVDF 膜放入待测一抗中,4℃孵育过夜,TBST 缓</br>冲液洗膜。 将膜移入二抗中,室温 1 h,洗膜。 电化学发光液浸</br>润,曝光、洗片,应用扫描仪和图像仪分析白蛋白条带。</br>3. 统计学处理:所有实验均重复 3 次,应用 SPSS 17. 0 软件</br>进行数据处理,数据以 x-± s 表示,多组间比较行单因素方差分</br>析,组间两两比较行 LSD 检验,P<0. 05 为差异具有显著性。</br>二、 结果</br>1. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖:随着<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>浓度升高,A 值逐</br>渐增加,表明<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖能力依次升高(P<0. 05,表 1)。</br>表 1  不同浓度<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>对 MC3T3-E1 细胞增殖的影响(x-± s)</br><mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark></br>(μmol / L) 样本数 A 值</br>增殖率</br>(% )</br>空白 5 0. 30 ± 0. 13 -</br>0 5 1. 29 ± 0. 23 -</br>1 5 1. 42 ± 0. 78a 13. 1</br>10 5 1. 53 ± 0. 44a 24. 2</br>20 5 1. 60 ± 0. 20a 31. 3</br>注:空白组不加细胞和<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>;与 0 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>组比较,</br>aP<0. 05</br>2. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的凋亡:与对照组相比,经不同浓度<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>干预后<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的早期凋亡率逐渐下降,浓度越高,下</br>降幅度越明显(P<0. 05,表 2)。</br>3. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的 mRNA 表达:<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的 mRNA</br>表达量随着<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>浓度的增加而升高(P<0. 05,图 1 和图</br>2)。</br>4. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的蛋白表达:随着<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>浓度的<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">升高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>,</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达量逐渐下降,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达量逐渐升高,Bcl-2 / Bax 比</br>率逐渐上升(P<0. 05,图 3)。</br>表 2  不同浓度<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>对 MC3T3-E1 细胞凋亡的影响(x-± s)</br><mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark></br>(μmol / L) 样本数</br>早期凋亡率</br>(% )</br>0 3 19. 63 ± 1. 36</br>1 3 11. 20 ± 1. 41a</br>10 3 7. 90 ± 0. 40a</br>20 3 4. 70 ± 0. 38a</br>注:与 0 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>组比较,aP<0. 05</br>注:与 0 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>组比较,aP<0. 05</br>图 1  不同浓度<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">I型胶原蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>表达的影响</br>注:与 0 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>组比较,aP<0. 05</br>图 2  不同浓度<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>对<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨桥蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达的影响</br>注:<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>:抗凋亡蛋白;<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">凋亡蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>;与 0 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>组比</br>较,aP<0. 05</br>图 3  <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>对 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 蛋白表达的影响</br>三、 讨论</br><mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病性骨质疏松<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>是指<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>并发单位体积内<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨量减少<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>、</br><mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨组织微结构改变<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>、<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨强度降低<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>、<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">脆性增加<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>等易发生<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的一</br>种全身性、<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">代谢性骨病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>。 在先前的研究中发现,部分<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">降糖药<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>在</br>降低<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">血糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的同时可对<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨代谢<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>产生保护作用,进而减少<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>发生</br>率。 本研究结果显示,与对照组相比,1、10 和 20 μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>使 MC3T3-E1 细胞增殖率分别增加 13. 1% 、24. 2% 和</br>31. 3% ,提示<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>能够在<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">高糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>环境下刺激 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>增殖而可促进骨形成。</br>对 MC3T3-E1 细胞凋亡的相关研究发现,0、1、10 和 20</br>μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>组的早期凋亡率依次为 19. 63% 、11. 20% 、</br>7. 9% 、4. 7% 。 说明<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>能够抑制 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的凋亡。</br>本实验进一步检测了 MC3T3-E1 成骨细胞凋亡相关蛋白 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达水平。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 家族在调节细胞凋亡中起着尤为重要</br>的作用,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 作为细胞凋亡基因的代表,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 基因作为细胞生</br>存基因的代表,二者表达水平之间的平衡结果决定了细胞生存</br>还是凋亡。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 表达高于 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 时,Bax-Bax 同型二聚体占优</br>势,诱导细胞凋亡增加。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 表达水平高于 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 时,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax-Bax二聚体<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>解离,形成更稳定的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2-Bax 二聚体<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,从而中和了 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>诱导细胞凋亡的作用,使细胞得以存活[10] 。 先前研究发现<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">吡格列酮<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>可能通过调控 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax / Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达诱导<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>凋亡[11] 。</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">胰岛素样生长因子I<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">IGF-I<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>)主要通过调节 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的相对表达比例抑制细胞凋亡,从而调节<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨代谢<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>平衡[12] 。 本研究发现<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>的浓度越高,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达水平<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">越低<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达水平<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">越高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>,即 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> / <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 比率逐渐<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">升高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>,由此推</br>测<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>可能是通过上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> / <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 比率来抑制 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的凋亡。</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">碱性磷酸酶<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>(ALP)活性、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OCN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 等</br>的合成及矿化结节的形成都是<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>分化的特征性标志物。</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 是<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>合成和分泌的特异性功能蛋白,为衡量<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>成骨能力的一个重要指标。 Kanazawa 等[13] 发现<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">二甲双胍<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark></br>增加 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OCN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达。 马攀等[14]</br>发现<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列美脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>能够促进<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖,提高其 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">ALP<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的活性及</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OCN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的 mRNA 表达水平。 本研究显示<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>同样</br>能够增加 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达水平,且在一定范围内</br>具有浓度依赖性。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨桥蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>是磷酸化、糖基化的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">细胞外基质蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,是骨形成和骨重建的标志性蛋白之一。 在骨基质矿化开始</br>后,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的 mRNA 水平开始<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">升高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>,可见 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在骨矿</br>化过程中具有重要作用。 Srivastava 等[15] 发现<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">胰岛素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>能够通过</br>提高分化标志物基因 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">ALP<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">核心结合因子 α1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(RUNX2)</br>的表达进而诱导<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨髓间充质干细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>向<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>分化。 羟基磷</br>灰石释放出的钙能够促进 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">ALP<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨唾液酸蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的表达[16] 。 本实验发现加入不同浓度的<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>后,</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> mRNA 相对表达量呈剂量依赖性<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">升高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>。</br>由此推测<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>可能通过上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">COL-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OPN<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的表达促进</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的分化。</br>综上所述,在<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">高糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>环境下,在一定浓度范围内,<mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">格列苯脲<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark>能</br>够剂量依赖性促进 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖和分化,并通过上调</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-2<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> / <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bax<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 比率来抑制 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">MC3T3-E1 细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的凋亡。</div>"
      ],
      "text/plain": [
       "<data_utils.data_utils.Document at 0x7f4c83cb10b8>"
      ]
     },
     "execution_count": 4,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "train_docs[0]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 5,
   "metadata": {},
   "outputs": [],
   "source": [
    "num_cates = max(ent2idx.values()) + 1\n",
    "sent_len = 64\n",
    "vocab_size = 3000\n",
    "emb_size = 100\n",
    "sent_pad = 10\n",
    "sent_extrator = SentenceExtractor(window_size=sent_len, pad_size=sent_pad)\n",
    "train_sents = sent_extrator(train_docs)\n",
    "test_sents = sent_extrator(test_docs)\n",
    "\n",
    "train_data = Dataset(train_sents, cate2idx=ent2idx)\n",
    "train_data.build_vocab_dict(vocab_size=vocab_size)\n",
    "\n",
    "test_data = Dataset(test_sents, word2idx=train_data.word2idx, cate2idx=ent2idx)\n",
    "vocab_size = len(train_data.word2idx)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 6,
   "metadata": {},
   "outputs": [],
   "source": [
    "w2v_train_sents = []\n",
    "for doc in docs:\n",
    "    w2v_train_sents.append(list(doc.text))\n",
    "w2v_model = Word2Vec(w2v_train_sents, size=emb_size)\n",
    "\n",
    "w2v_embeddings = np.zeros((vocab_size, emb_size))\n",
    "for char, char_idx in train_data.word2idx.items():\n",
    "    if char in w2v_model.wv:\n",
    "        w2v_embeddings[char_idx] = w2v_model.wv[char]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 7,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "_________________________________________________________________\n",
      "Layer (type)                 Output Shape              Param #   \n",
      "=================================================================\n",
      "input_1 (InputLayer)         (None, 84)                0         \n",
      "_________________________________________________________________\n",
      "embedding_1 (Embedding)      (None, 84, 100)           300000    \n",
      "_________________________________________________________________\n",
      "bidirectional_1 (Bidirection (None, 84, 512)           731136    \n",
      "_________________________________________________________________\n",
      "crf_1 (CRF)                  (None, 84, 16)            8496      \n",
      "=================================================================\n",
      "Total params: 1,039,632\n",
      "Trainable params: 739,632\n",
      "Non-trainable params: 300,000\n",
      "_________________________________________________________________\n"
     ]
    }
   ],
   "source": [
    "seq_len = sent_len + 2 * sent_pad\n",
    "model = build_lstm_crf_model(num_cates, seq_len=seq_len, vocab_size=vocab_size, \n",
    "                             model_opts={'emb_matrix': w2v_embeddings, 'emb_size': 100, 'emb_trainable': False})\n",
    "model.summary()"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 8,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "train_X.shape (47577, 84)\n",
      "train_y.shape (47577, 84, 1)\n"
     ]
    }
   ],
   "source": [
    "train_X, train_y = train_data[:]\n",
    "print('train_X.shape', train_X.shape)\n",
    "print('train_y.shape', train_y.shape)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## train model"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 9,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "Epoch 1/10\n",
      "47577/47577 [==============================] - 208s 4ms/step - loss: 0.3134 - acc: 0.8861\n",
      "Epoch 2/10\n",
      "47577/47577 [==============================] - 211s 4ms/step - loss: 0.1573 - acc: 0.9194\n",
      "Epoch 3/10\n",
      "47577/47577 [==============================] - 211s 4ms/step - loss: 0.1104 - acc: 0.9303\n",
      "Epoch 4/10\n",
      "47577/47577 [==============================] - 211s 4ms/step - loss: 0.0837 - acc: 0.9388\n",
      "Epoch 5/10\n",
      "47577/47577 [==============================] - 210s 4ms/step - loss: 0.0653 - acc: 0.9464\n",
      "Epoch 6/10\n",
      "47577/47577 [==============================] - 211s 4ms/step - loss: 0.0499 - acc: 0.9539\n",
      "Epoch 7/10\n",
      "47577/47577 [==============================] - 211s 4ms/step - loss: 0.0370 - acc: 0.9605\n",
      "Epoch 8/10\n",
      "47577/47577 [==============================] - 210s 4ms/step - loss: 0.0248 - acc: 0.9668\n",
      "Epoch 9/10\n",
      "47577/47577 [==============================] - 211s 4ms/step - loss: 0.0142 - acc: 0.9714\n",
      "Epoch 10/10\n",
      "47577/47577 [==============================] - 211s 4ms/step - loss: 0.0032 - acc: 0.9762\n"
     ]
    },
    {
     "data": {
      "text/plain": [
       "<keras.callbacks.History at 0x7f4cea770dd8>"
      ]
     },
     "execution_count": 9,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "model.fit(train_X, train_y, batch_size=64, epochs=10)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## make prediction"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 10,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "2688/2688 [==============================] - 8s 3ms/step\n"
     ]
    }
   ],
   "source": [
    "test_X, _ = test_data[:]\n",
    "preds = model.predict(test_X, batch_size=64, verbose=True)\n",
    "pred_docs = make_predictions(preds, test_data, sent_pad, docs, idx2ent)"
   ]
  },
  {
   "cell_type": "markdown",
   "metadata": {},
   "source": [
    "## evaluate on validatation set"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 11,
   "metadata": {},
   "outputs": [
    {
     "name": "stdout",
     "output_type": "stream",
     "text": [
      "f_score:  0.7672501873169403\n",
      "precision:  0.7627302275189599\n",
      "recall:  0.7718240372755927\n"
     ]
    }
   ],
   "source": [
    "f_score, precision, recall = Evaluator.f1_score(test_docs, pred_docs)\n",
    "print('f_score: ', f_score)\n",
    "print('precision: ', precision)\n",
    "print('recall: ', recall)"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 12,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div class=\"entities\" style=\"line-height: 2.5\"><mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">代谢性骨病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark></br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖分化</br>和<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白 5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1 基因<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>表达</br>的影响</br>熊燕琴  孙向华  张克勤  周筠  张秀珍  雷涛</br>[摘要]   目的  研究不同浓度<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> MC3T3-E1 增殖分化及</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白 5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1 基因<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>表达的可能影响,探讨 Wnt 信号通路是否参与了<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖分化的调节。 方法 在小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>株 MC3T3-E1 培养液中加入 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">0. 1 mg / ml<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 的不同浓度的</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,分别培养 24、48、72 h 后应用 CCK-8 检测其对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的影响,采用 ELISA 法检测<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平;采用 realtime <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 方法检测<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1 基因<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>表达的影响。 结果 在</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 糖化浓度为 <mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">5. 3%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark> 24 h 时,明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,与对照组比较,差异具有统计学意义(P<0. 01),</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 糖化越高,对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的抑制越明显,在一定的时间和浓度范围内<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的作</br>用呈剂量及时间依赖性;与对照组比较,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达,差异具有统计学意</br>义(P<0. 01),<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达的作用在一定程度上具有剂量及作用时间依赖性;<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">5. 3%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 48 h 时明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达水平,显著上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达水平,与对照</br>组比较,差异具有统计学意义(P<0. 01)。 结论 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 显著抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖和分化,这可能与</br>Wnt 信号通路中 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 及 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1 基因<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>表达有关。</br>[关键词]   <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>; <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>; <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>相关蛋白 5; DKK1; Wnt 信号通路</br>Effects of glycated low density lipoprotein on the proliferation and differentiation and expression of low-</br>density lipoprotein receptor-related protein-5 mRNA, dickkopf-1 mRNA in mouse osteoblasts Xiong</br>Yanqin*, Sun Xianghua, Zhang Keqin, Zhou Yun, Zhang Xiuzheng, Lei Tao. *Department of Endocrinology,</br>Shanghai Tongji Hospital, Shanghai 200065, China</br>[Abstract]   Objective   The aim of this study was to investigate the possible effect of glycated low density</br>lipoprotein ( <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>) on the proliferation, differentiation, and expression of low-density lipoprotein receptor-related</br>protein 5 (LRP5) mRNA, dickkopf-1 (DKK1) mRNA in mouse osteoblasts(MC3T3-E1 cells) . Whether the Wnt</br>signaling pathway was involved in the above process was explored else. Methods Mouse MC3T3-E1 cells were</br>cultured with various concentrations of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>(glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> level was 2. 4% ,5. 3% ,8. 7% ,13. 9% ) for 24,</br>48, 72 h. Proliferation of MC3T3-E1 cell was measured by CCK-8, the osteocalcin level in the medium was</br>determined by ELISA and the expression of LRP5 mRNA, DKK1 mRNA was measured by realtime PCR. Results</br>After cells being incubated with 5. 3% of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> for 24 h, the inhibition of MC3T3-E1 cells was more marked</br>than that in control group(P<0. 01) . The higher glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> level, the severer the inhibition. The effect of <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on</br>the MC3T3-E1 cell proliferation was time- and dose-dependent under certain conditions. Osteocalcin level in cell</br>culture fluid with glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> was lowered significantly compared with control group. Meanwhile, the expression of</br>DKK1 mRNA was increased significantly but expression of LRP5 mRNA decreased (P<0. 01) in MC3T3-E1 cells</br>cultured with 5. 3% of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> for 24 h. Conclusions Proliferation and differentiation of the osteoblasts in mice</br>can be inhibited significantly by glycated LDL. The possible mechanism in the role played by glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on the</br>proliferation and differentiation in MC3T3-E1 cells seems to be related to expression of LRP5 mRNA, DKK1 mRNA in</br>the Wnt signaling pathway.</br>[Key words]   Low density lipoprotein; Osteoblast; Low density lipoprotein receptor-related protein 5;</br>Dickkopf-1; Wnt signaling pathway</br>(Chin J Endocrinol Metab, 2014, 30: 654-658)</br><mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>(osteoporosis)是一种以<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨量减少<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>和<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨微结构破坏<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>为特征,导致<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨强度下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>,<mark class=\"entity\" style=\"background: #ff8197; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质脆性增加<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Reason</span></mark>和</br>易于<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">代谢性骨病综合症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>。 随着我国人口的老龄</br>化,<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的患病率明显增加,因此对于<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的防治非常重要。 <mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>是常见病,除<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖代谢紊乱<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark></br>引起<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">血糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark><mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">增高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>外,常同时伴有脂代谢的紊乱。 研究表</br>明<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>( low density lipoprotein, <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">胆固醇<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>和<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>之间关系密切[1,2];但 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>下可</br>发生糖化,而 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 糖化后对骨代谢的影响如何,目前</br>研究罕见[3,4],其确切机制尚不明确。 Wnt 通路在骨形</br>成和分化中起着重要的作用, <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白 5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> ( low density lipoprotein receptor-related protein 5,</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)是 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 超家族成员,它是 Wnt 的共受体,它的</br>增加或减少可导致骨量的增加或减少,而 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 是</br>Wnt 通道的抑制因子,能抑制骨形成。 因此本研究拟</br>检测 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 糖化后对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖、分化能力的影响,</br>同时测定糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表</br>达情况,以分析<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>作用的可能机</br>制。</br>材料和方法</br>一、 材料</br>小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨样细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> MC3T3-E1 购自中科院上海细胞</br>研究所医学细胞库;无酚红 α-MEM 培养液和胎牛血</br>清购自美国 Gibco 公司;<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 购自美国 Millipore 公司;</br>氨基苯硼酸琼脂糖凝胶亲和层析柱由美国 Sigma 公司</br>提供。 小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>( osteocalcin) ELISA Kit 购于美国</br>IBL 公司;CCK-8 试剂购自南京凯基生物科技发展公</br>司; TRIzol 购 于 Invitrogen 公 司, PrimeScriptTM RT</br>reagent Kit(Perfect Real Time) DRR037A 购于 Takara 公</br>司,SYBR Premix Ex Taq(Perfect Real Time) DRR041A</br>购于 Takara 公司,引物由上海生工生物有限公司合</br>成。 Synergy2 多功能酶标仪为 BioTek 公司产品,PTC-</br>200PCR 仪为 MJ RESEARCH 公司产品,7900HT 荧光</br>定量仪为 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">ABI<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 公司产品。</br>二、 方法</br>1. 细胞培养:MC3T3-E1 细胞培养于含 10% 胎牛</br>血清的无酚红 α-MEM 培养液中,隔天换液,2 ~ 3 d 传</br>代 1 次。</br>2. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的糖化:参照 Sima 等[5] 的方法,在无菌的</br>条件下,将 2 mg / ml 的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 与不同浓度葡萄糖液(5、</br>20、100、200 mmol / L)在 37℃用含 1 mg / ml EDTA 和 10</br>μmol / L BHT 抗氧化的情况下孵育 4 周,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 用</br>PBS 液透析后备用。</br>3. <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 糖化的测定:采用氨基苯硼酸琼脂糖凝胶</br>亲和层析法。 亲和层析柱用平衡液 5 ml 平衡后加入</br>含<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的溶液 0. 05 ml,再加入平衡液 0. 1 ml,10</br>min 后加入 2. 85 ml 平衡液洗脱,弃掉滴出的含非<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的液体。 最后加入洗脱液 2 ml,并收集洗脱的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 于试管内,在试管中加入胆固醇酶试剂后在</br>500 nm 处测定<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL 胆固醇<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的吸光度,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>的值用它所占总 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的百分数表示。 批内 CV 为</br>4. 2% ,批间 CV 为 4. 9% 。</br>4. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖影响:细胞生长</br>至 80% ~ 90% 汇合处,用<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">胰酶<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>消化计数。 以每孔</br>5 000 个细胞接种至 96 孔板,常规培养待细胞贴壁后,</br>弃去培养液,加入 0. 1 mg / ml 的单纯 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和含不同浓</br>度<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的培养液。 设空白对照,空白对照不加</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,只加培养液。 培养处理细胞 24、48、72 h 后,加入</br>CCK-8 试剂 10 滋l,继续放入培养箱孵育 1 h 后,在酶联</br>免疫检测仪上检测 450 nm 波长处各孔的吸光度(OD)</br>值。 并计算<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 抑制率(% )。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 抑制率</br>(% )= (对照组 OD 值-<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 或单纯 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> OD 值) /</br>对照组 OD 值×100% 。</br>5. 细胞培养液中<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平的测定:细胞传代后</br>接种于 6 孔板中,每孔约 105 个细胞,当细胞融合达</br>70%时同上分别加入 0. 1 mg / ml 的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">单纯 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和含不同</br>浓度<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的培养液。 设空白对照,空白对照不加</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,只加培养液,继续培养 24、48 和 72 h 收集细胞培</br>养上清,吸取上清液,ELISA 法测定<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>上清液中</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的水平,用 bradford 方法测定<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">细胞内总蛋白含量<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>以校正<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>值。</br>6. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 基因 mRNA 的表达:采</br>用 RT-PCR 法。 引物合成与设计见表 1,由上海生工公</br>司合成。 将各组细胞分别加入 0. 1 mg / ml 的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">单纯 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>和含不同浓度<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的培养液。 设空白对照, 空白</br>表 1  基因和引物序列</br>Tab 1  Genes and Sequences of primers</br>基因</br>Gene</br>正义链</br>Sense</br>(5'-3')</br>反义链</br>Antisense</br>(3忆-5忆)</br>产物大小</br>Product size</br>(bp)</br>β-actin AGCGAGCATCCCCCAAAGTT GGGCACGAAGGCTCATCATT 250</br>DKK1 TCACACCAAAGGACAAGAAGG CTTGGACCAGAAGTGTCTTGC 88</br>LRP5 GACTGTGCTGATGGGTCTGAT GACGAAGAGGGAGAGGATGAT 120</br>注:LRP5:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>相关蛋白 5 Low density lipoprotein receptor-related protein 5</br>对照为不加 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的培养液,培养细胞继续培养 24、48</br>和 72 h 后,弃去培养液,按常规方法提取总 RNA,采取</br>逆转录试剂盒将 RNA 合成 cDNA,再进行荧光定量</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>,检测各组细胞 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达情况,每</br>组设非糖化的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对照组和空白对照。 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 反应条</br>件如下:94℃预变性 4 min;94℃变性 20 s;60℃退火 30</br>s;72℃延伸 30 s 循环 35 次;72℃检测信号;扩增完毕</br>后进行溶解曲线分析,以确定反应产物的单一性。 每</br>组样品重复测量 3 次,各组比较采用 2-△△CT值对基因的</br>表达量进行相对分析。</br>三、 统计学处理</br>所有实验均重复检测 3 次,取平均值,计量资料采</br>用 x-± s 的形式。 采用 SPSS 17. 0 统计软件,各种数据</br>经过正态检验和方差齐性检验过后,采用单因素方差</br>分析或 t 检验进行统计学分析,P<0. 05 为差异有统计</br>学意义。</br>结果</br>一、 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的糖化值</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 与 不 同 浓 度 葡 萄 糖 液 ( 5、 20、 100、 200</br>mmol / L)孵育 4 周,测定 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的糖化值分别为 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">2. 4%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 、</br><mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">5. 3%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 、<mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">8. 7%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark>和 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">13. 9%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 。</br>二、 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增值影响</br>实验结果表明在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark> 浓度为 5. 3%时,</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖受到抑制,与<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">单纯 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 比较,差异具</br>有统计学意义(P<0. 01),且糖化浓度越高,抑制越明</br>显。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在作用时间为 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">48 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark>,浓度为 5. 3%时,同</br>样可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,随着浓度的增加抑制作用</br>有所增加但幅度有所下降。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">72 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 时浓度</br>为 5. 3%时,同样可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,但随着浓度</br>的增加其对细胞增殖的抑制作用不再增加。 而<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 2. 4%时各时间段均不增加细胞的增殖,与单</br>纯 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 比较无统计学差异(图 1)。</br>三、 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>培养液中<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平的</br>影响</br>ELISA 实验结果显示<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 浓度为</br>5. 3%时,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>培养液中的<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">明显下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>,</br>与对照组比较,差异具有统计学意义(P<0. 01),且糖</br>化浓度越高,下降越明显。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在作用时间为 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">48h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 浓度为 5. 3%时,同样可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,随着</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 浓度的增加<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平下降越明显。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">72 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 浓度为 5. 3%时,可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的骨钙</br>注:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;Gly-:糖化 Glycated;vs <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>,aP<0. 01;vs 2. 4% <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Gly-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,bP<0. 01</br>图 1  <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的影响</br>Fig 1  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on proliferation of MC3T3 osteoblasts</br>注:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;Gly-:糖化 Glycated;vs <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>,aP<0. 01;vs 2. 4% <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Gly-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,bP<0. 01</br>图 2  <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的影响</br>Fig 2  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on osteocalcin levels of MC3T3 osteoblasts</br>注:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;LRP5:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>相关蛋白 5 Low density lipoprotein receptor-related protein 5;Gly-:糖化 Glycated;vs</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>,aP<0. 01;vs 2. 4% <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Gly-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,bP<0. 01</br>图 3  <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> LRP5 mRNA 表达的影响</br>Fig 3  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on proliferation of LRP5 mRNA in osteoblasts</br>注:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>: <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;CON:对照 Control;Gly-:糖化 Glycated;vs <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>,aP<0. 01;vs 2. 4% <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Gly-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,bP<0. 01</br>图 4  <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> DKK1 mRNA 表达的影响</br>Fig 4  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on expression of DKK1 mRNA in osteoblasts</br>素水平,但随着浓度的增加其对细胞<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的抑制作</br>用不再增加。 而<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 2. 4%时各时间段均不增</br>加细胞的增殖,与<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">单纯 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 比较无统计学差异。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 与<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">单纯 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 比较,在浓度 5. 3% ,时间为 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">48 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 时</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark><mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>(P<0. 01)。 提示<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达具有一定的抑制作用(图 2)。</br>四、 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 和</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达的影响</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 浓度为 5. 3% 时明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达水平,显著上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>mRNA 表达水平,与对照组比较,差异具有统计学意义</br>(P<0. 01),糖化浓度越高则幅度越明显。 单因素方差</br>分析显示当作用时间为 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">48 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 和 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">72 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark>,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 各组</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 相对表达量虽然<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>但已较 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 有所减</br>弱,而 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 相对表达量上调幅度也明显减少。</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">单纯 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">2. 4%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 组与对照组比较无论是</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 的表达还是 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达均无统计</br>学差异(图 3、图 4)。</br>讨论</br>骨重建由骨生成和骨吸收两部分构成,是一个动</br>态的过程。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>是骨形成、生长、发育的重要细</br>胞,其来源于<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨髓<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>基质的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">间质细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,在骨形成过程中经</br>历增殖、分化成熟和基质钙化三个阶段,任何一个阶段</br>出现异常都会对骨组成和骨量产生重要的影响。 目前</br>有关 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 与骨代谢关系的研究结果存在有分歧,一些</br>研究表明 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 水平与<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨密度<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>呈负相关[6];也有研究未</br>显示两者的相关性[7]。 这可能涉及 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的成分不一</br>和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 不同修饰,尤其是<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>高糖下极易发生 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>的糖化,但<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 是否对骨代谢有影响,尤其是对</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>是否有直接影响以及如何影响未见报道。 本</br>研究发现当<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 达到 5. 3% 时,明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,且<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的抑制作用在</br>一定程度上呈剂量及作用时间依赖性,但随着时间延</br>长,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 增高到一定程度则不再抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的</br>增殖。 这与氧化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的作用相似,Brodeur</br>等[8]观察到 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">10 ~ 50 μg / ml<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">氧化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>( oxidized low</br>density lipoprotein, <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Ox-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)可促进<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,</br>而 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">150 μg / ml<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 浓度以上的 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Ox-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 可杀死细胞并诱导</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的凋亡。 Klein 等[9]发现 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">氧化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可</br>诱导 Saos2 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>凋亡,同时 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可上调促凋亡基</br>因 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-Xs<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和下调抗凋亡 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Src 激酶<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>活性,说明 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 及其</br>修饰化在<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中具有多重功能。</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>在骨矿化峰期之后才出现积聚,由<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>合成并分泌,不受骨吸收因素的影响,因此<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>可</br>以了解<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>特别是新形成的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的活动状</br>态,反映了<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的活性。 临床发现<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>患者<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">血糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>控制不佳时<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">明显升高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>[10];但机制未明。</br>本研究发现 5. 3% <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 时明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>表达,随着 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 浓度和作用时间的增</br>加,抑制作用不断增强,而正常的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> (糖化</br>2. 4% )与<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">非糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 没有抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的表</br>达,说明增高<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的表</br>达,提示<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 增高可能引起骨形成的下降。</br>本研究结果显示 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">5. 3%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 及其以上的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在</br><mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark>、<mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">48<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 和 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">72 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 均明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA</br>表达,显著上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达,但正常<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">非糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达没有</br>影响,提示过度<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可通过 Wnt 信号通路 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP-5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>及其抑制剂 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达,进而影响<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖</br>和分化。 而 Wnt 通路可调节<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的分化、骨基质</br>的形成及矿化、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">破骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的功能和骨吸收等多个环</br>节[11]。 研究显示 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可通过 Wnt / LRP5 / β-连环蛋</br>白途径直接调节<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>功能及骨量[12]。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 是</br>由细胞分泌的生物活性物质,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可直接与 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP 受体<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>结合, 或者与其跨膜受体 Kremen 结合后再与</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5 / 6<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 结合形成三聚体,诱导细胞内吞,减少细胞膜</br>上的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5 / 6<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,从而阻断了 Wnt 信号向胞内的传递[13]。</br>此外过度表达的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨髓基质细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>向<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>分化,使<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>数量减少并抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨基质<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的矿化</br>及<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>后的修复[14]。 本研究结果显示<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 时明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达,显著上</br>调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达,但正常<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">非糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>对 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达没有影响,提示过</br>度<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖和分化的抑制作用可能</br>与 Wnt 信号通路 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 及其抑制剂 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达有一定关系,其机制还需进一步进行探讨。</div>"
      ],
      "text/plain": [
       "<data_utils.data_utils.Document at 0x7f49601f84a8>"
      ]
     },
     "execution_count": 12,
     "metadata": {},
     "output_type": "execute_result"
    }
   ],
   "source": [
    "sample_doc_id = list(pred_docs.keys())[0]\n",
    "test_docs[sample_doc_id]"
   ]
  },
  {
   "cell_type": "code",
   "execution_count": 13,
   "metadata": {},
   "outputs": [
    {
     "data": {
      "text/html": [
       "<div class=\"entities\" style=\"line-height: 2.5\"><mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">代谢性骨病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark></br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖分化</br>和<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白 5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 基因表达</br>的影响</br>熊燕琴  孙向华  张克勤  周筠  张秀珍  雷涛</br>[摘要]   目的  研究不同<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">浓度糖化低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>(糖化 LDL)对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> MC3T3-E1 增殖分化及</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白 5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>(<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 基因表达的可能影响,探讨 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Wnt 信号通路<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>是否参与了糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖分化的调节。 方法 在小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>株 MC3T3-E1 培养液中加入 0. 1 mg / ml 的不同浓度的</br>糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>,分别培养 24、48、72 h 后应用 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">CCK-8<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 检测其对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的影响,采用 ELISA 法检测<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平;采用 realtime <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 方法检测糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 基因表达的影响。 结果 在</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 糖化浓度为 5. 3% 24 h 时,明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,与对照组比较,差异具有统计学意义(P<0. 01),</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 糖化越高,对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的抑制越明显,在一定的时间和浓度范围内糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的作</br>用呈剂量及时间依赖性;与对照组比较,<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达,差异具有统计学意</br>义(P<0. 01),糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达的作用在一定程度上具有剂量及作用时间依赖性;5. 3% 糖</br>化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 48 h 时明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达水平,显著上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达水平,与对照</br>组比较,差异具有统计学意义(P<0. 01)。 结论 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 显著抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖和分化,这可能与</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Wnt 信号通路<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 及 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 基因表达有关。</br>[关键词]   <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>; <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>; <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 5; <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>; Wnt 信号通路</br>Effects of glycated low density lipoprotein on the proliferation and differentiation and expression of low-</br>density lipoprotein receptor-related protein-5 mRNA, dickkopf-1 mRNA in mouse osteoblasts Xiong</br>Yanqin*, Sun Xianghua, Zhang Keqin, Zhou Yun, Zhang Xiuzheng, Lei Tao. *Department of Endocrinology,</br>Shanghai Tongji Hospital, Shanghai 200065, China</br>[Abstract]   Objective   The aim of this study was to investigate the possible effect of glycated low density</br>lipoprotein ( <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>) on the proliferation, differentiation, and expression of low-density lipoprotein receptor-related</br>protein 5 (LRP5) mRNA, <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">dickkopf-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> (DKK1) mRNA in mouse osteoblasts(MC3T3-E1 cells) . Whether the Wnt</br>signaling pathway was involved in the above process was explored else. Methods Mouse MC3T3-E1 cells were</br>cultured with various concentrations of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>(glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> level was 2. 4% ,5. 3% ,8. 7% ,13. 9% ) for 24,</br>48, 72 h. Proliferation of MC3T3-E1 cell was measured by CCK-8, the osteocalcin level in the medium was</br>determined by ELISA and the expression of LRP5 mRNA, DKK1 mRNA was measured by realtime PCR. Results</br>After cells being incubated with 5. 3% of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> for 24 h, the inhibition of MC3T3-E1 cells was more marked</br>than that in control group(P<0. 01) . The higher glycated LDL level, the severer the inhibition. The effect of <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on</br>the MC3T3-E1 cell proliferation was time- and dose-dependent under certain conditions. Osteocalcin level in cell</br>culture fluid with glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> was lowered significantly compared with control group. Meanwhile, the expression of</br>DKK1 mRNA was increased significantly but expression of LRP5 mRNA decreased (P<0. 01) in MC3T3-E1 cells</br>cultured with 5. 3% of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> for 24 h. Conclusions Proliferation and differentiation of the osteoblasts in mice</br>can be inhibited significantly by glycated LDL. The possible mechanism in the role played by glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on the</br>proliferation and differentiation in MC3T3-E1 cells seems to be related to expression of LRP5 mRNA, DKK1 mRNA in</br>the Wnt signaling pathway.</br>[Key words]   Low density lipoprotein; Osteoblast; Low density lipoprotein receptor-related protein 5;</br>Dickkopf-1; Wnt signaling pathway</br>(Chin J Endocrinol Metab, 2014, 30: 654-658)</br><mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>(osteoporosis)是一种以<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨量减少<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Symptom</span></mark>和<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨微结构破坏<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Symptom</span></mark>为特征,导致<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨强度下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Symptom</span></mark>,<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质脆性增加<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Symptom</span></mark>和</br>易于<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">代谢性骨病综合症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>。 随着我国人口的老龄</br>化,<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的患病率明显增加,因此对于<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松症<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>的防治非常重要。 <mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>是常见病,除<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖代谢紊乱<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark></br>引起<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">血糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark><mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">增高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>外,常同时伴有<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">脂代谢的紊乱<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>。 研究表</br>明<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>( low density lipoprotein, <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>)胆固醇</br>和<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨质疏松<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>之间关系密切[1,2];但 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>下可</br>发生糖化,而 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 糖化后对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>代谢的影响如何,目前</br>研究罕见[3,4],其确切机制尚不明确。 Wnt 通路在<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>形</br>成和分化中起着重要的作用, <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白 5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> ( low density lipoprotein receptor-related protein 5,</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)是 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL 超家族<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>成员,它是 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Wnt<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的共受体,它的</br>增加或减少可导致<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨量<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的增加或减少,而 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 是</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Wnt 通道<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的抑制因子,能抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>形成。 因此本研究拟</br>检测 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 糖化后对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖、<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">分化能力<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的影响,</br>同时测定糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表</br>达情况,以分析糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>作用的可能机</br>制。</br>材料和方法</br>一、 材料</br>小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨样细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> MC3T3-E1 购自中科院上海细胞</br>研究所医学细胞库;无酚红 α-MEM 培养液和胎牛血</br>清购自美国 Gibco 公司;LDL 购自美国 Millipore 公司;</br>氨基苯硼酸琼脂糖凝胶亲和层析柱由美国 Sigma 公司</br>提供。 小鼠<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>( osteocalcin) ELISA Kit 购于美国</br>IBL 公司;CCK-8 试剂购自南京凯基生物科技发展公</br>司; TRIzol 购 于 Invitrogen 公 司, PrimeScriptTM RT</br>reagent Kit(Perfect Real Time) DRR037A 购于 Takara 公</br>司,SYBR Premix Ex Taq(Perfect Real Time) DRR041A</br>购于 Takara 公司,引物由上海生工生物有限公司合</br>成。 Synergy2 多功能酶标仪为 BioTek 公司产品,PTC-</br>200PCR 仪为 MJ RESEARCH 公司产品,7900HT 荧光</br>定量仪为 ABI 公司产品。</br>二、 方法</br>1. 细胞培养:MC3T3-E1 细胞培养于含 10% 胎牛</br>血清的无酚红 α-MEM 培养液中,隔天换液,2 ~ 3 d 传</br>代 1 次。</br>2. LDL 的糖化:参照 Sima 等[5] 的方法,在无菌的</br>条件下,将 2 mg / ml 的 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 与不同浓度葡萄糖液(5、</br>20、100、200 mmol / L)在 37℃用含 1 mg / ml EDTA 和 10</br>μmol / L <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">BHT<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark> 抗氧化的情况下孵育 4 周,糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 用</br>PBS 液透析后备用。</br>3. <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL 糖化<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的测定:采用氨基苯硼酸琼脂糖凝胶</br>亲和层析法。 亲和层析柱用平衡液 5 ml 平衡后加入</br>含糖化 LDL 的溶液 0. 05 ml,再加入平衡液 0. 1 ml,10</br>min 后加入 2. 85 ml 平衡液洗脱,弃掉滴出的含非糖化</br>LDL 的液体。 最后加入洗脱液 2 ml,并收集洗脱的糖</br>化 LDL 于试管内,在试管中加入胆固醇酶试剂后在</br>500 nm 处测定糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">胆固醇<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的吸光度,糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark></br>的值用它所占总 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的百分数表示。 批内 CV 为</br>4. 2% ,批间 CV 为 4. 9% 。</br>4. <mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖影响:细胞生长</br>至 80% ~ 90% 汇合处,用胰酶消化计数。 以每孔</br>5 000 个细胞接种至 96 孔板,常规培养待细胞贴壁后,</br>弃去培养液,加入 0. 1 mg / ml 的单纯 LDL 和含不同浓</br>度糖化 LDL 的培养液。 设空白对照,空白对照不加</br>LDL,只加培养液。 培养处理细胞 24、48、72 h 后,加入</br>CCK-8 试剂 10 滋l,继续放入培养箱孵育 1 h 后,在酶联</br>免疫检测仪上检测 450 nm 波长处各孔的吸光度(OD)</br>值。 并计算糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 抑制率(% )。 糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 抑制率</br>(% )= (对照组 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OD<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 值-糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 或单纯 LDL OD 值) /</br>对照组 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">OD<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 值×100% 。</br>5. 细胞培养液中<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平的测定:细胞传代后</br>接种于 6 孔板中,每孔约 105 个细胞,当细胞融合达</br>70%时同上分别加入 0. 1 mg / ml 的单纯 LDL 和含不同</br>浓度糖化 LDL 的培养液。 设空白对照,空白对照不加</br>LDL,只加培养液,继续培养 24、48 和 72 h 收集细胞培</br>养上清,吸取上清液,ELISA 法测定<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>上清液中</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的水平,用 bradford 方法测定细胞内<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">总蛋白含<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark></br>量以校正<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>值。</br>6. <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1 基因<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 的表达:采</br>用 RT-PCR 法。 引物合成与设计见表 1,由上海生工公</br>司合成。 将各组细胞分别加入 0. 1 mg / ml 的单纯 LDL</br>和含不同浓度糖化 LDL 的培养液。 设空白对照, 空白</br>表 1  基因和引物序列</br>Tab 1  Genes and Sequences of primers</br>基因</br>Gene</br>正义链</br>Sense</br>(5'-3')</br>反义链</br>Antisense</br>(3忆-5忆)</br>产物大小</br>Product size</br>(bp)</br>β-actin AGCGAGCATCCCCCAAAGTT GGGCACGAAGGCTCATCATT 250</br>DKK1 TCACACCAAAGGACAAGAAGG CTTGGACCAGAAGTGTCTTGC 88</br>LRP5 GACTGTGCTGATGGGTCTGAT GACGAAGAGGGAGAGGATGAT 120</br>注:LRP5:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 5 Low density lipoprotein receptor-related protein 5</br>对照为不加 LDL 的培养液,培养细胞继续培养 24、48</br>和 72 h 后,弃去培养液,按常规方法提取总 RNA,采取</br>逆转录试剂盒将 RNA 合成 cDNA,再进行荧光定量</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>,检测各组细胞 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达情况,每</br>组设非糖化的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对照组和空白对照。 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">PCR<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 反应条</br>件如下:94℃预变性 4 min;94℃变性 20 s;60℃退火 30</br>s;72℃延伸 30 s 循环 35 次;72℃检测信号;扩增完毕</br>后进行溶解曲线分析,以确定反应产物的单一性。 每</br>组样品重复测量 3 次,各组比较采用 2-△△CT值对基因的</br>表达量进行相对分析。</br>三、 统计学处理</br>所有实验均重复检测 3 次,取平均值,计量资料采</br>用 x-± s 的形式。 采用 SPSS 17. 0 统计软件,各种数据</br>经过正态检验和方差齐性检验过后,采用单因素方差</br>分析或 t 检验进行统计学分析,P<0. 05 为差异有统计</br>学意义。</br>结果</br>一、 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的糖化值</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 与 不 同 浓 度 葡 萄 糖 液 ( 5、 20、 100、 200</br>mmol / L)孵育 4 周,测定 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的糖化值分别为 2. 4% 、</br>5. 3% 、8. 7%和 13. 9% 。</br>二、 糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增值影响</br>实验结果表明在 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24 h 糖化<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 浓度为 5. 3%时,</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖受到抑制,与单纯 LDL 比较,差异具</br>有统计学意义(P<0. 01),且糖化浓度越高,抑制越明</br>显。 糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在作用时间为 48 h,浓度为 5. 3%时,同</br>样可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,随着浓度的增加抑制作用</br>有所增加但幅度有所下降。 糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 72 h 时浓度</br>为 <mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">5. 3%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>时,同样可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,但随着浓度</br>的增加其对细胞增殖的抑制作用不再增加。 而糖化</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 2. 4%时各时间段均不增加细胞的增殖,与单</br>纯 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 比较无统计学差异(图 1)。</br>三、 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>培养液中<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平的</br>影响</br>ELISA 实验结果显示糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 24 h 浓度为</br>5. 3%时,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>培养液中的<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">明显下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>,</br>与对照组比较,差异具有统计学意义(P<0. 01),且糖</br>化浓度越高,下降越明显。 糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在作用时间为 48</br>h 浓度为 5. 3%时,同样可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,随着</br>糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 浓度的增加<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平下降越明显。 糖化</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 72 h 浓度为 <mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">5. 3%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>时,可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark></br>注:LDL:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;Gly-:糖化 Glycated;vs LDL,aP<0. 01;vs 2. 4% Gly-LDL,bP<0. 01</br>图 1  糖化 LDL 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的影响</br>Fig 1  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on proliferation of MC3T3 osteoblasts</br>注:LDL:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;Gly-:糖化 Glycated;vs LDL,aP<0. 01;vs 2. 4% Gly-LDL,bP<0. 01</br>图 2  糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的影响</br>Fig 2  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on osteocalcin levels of MC3T3 osteoblasts</br>注:LDL:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;LRP5:<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白相关蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 5 Low density lipoprotein receptor-related protein 5;Gly-:糖化 Glycated;vs</br>LDL,aP<0. 01;vs 2. 4% Gly-LDL,bP<0. 01</br>图 3  糖化 LDL 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达的影响</br>Fig 3  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on proliferation of LRP5 mRNA in osteoblasts</br>注:LDL: <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">低密度脂蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> Low density lipoprotein;CON:对照 Control;Gly-:糖化 Glycated;vs LDL,aP<0. 01;vs 2. 4% Gly-LDL,bP<0. 01</br>图 4  糖化 LDL 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达的影响</br>Fig 4  The effect of glycated <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> on expression of DKK1 mRNA in osteoblasts</br>素水平,但随着浓度的增加其对细胞<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的抑制作</br>用不再增加。 而<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 2. 4%时各时间段均不增</br>加细胞的增殖,与单纯 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 比较无统计学差异。 糖化</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 与单纯 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 比较,在浓度 5. 3% ,时间为 48 h 时</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark><mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">下降<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>(P<0. 01)。 提示糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达具有一定的抑制作用(图 2)。</br>四、 糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对小鼠<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 和</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达的影响</br>糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 24 h 浓度为 5. 3% 时明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达水平,显著上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>mRNA 表达水平,与对照组比较,差异具有统计学意义</br>(P<0. 01),糖化浓度越高则幅度越明显。 单因素方差</br>分析显示当作用时间为 48 h 和 72 h,糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 各组</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 相对表达量虽然下降但已较 24 h 有所减</br>弱,而 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 相对表达量上调幅度也明显减少。</br>单纯 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 和 2. 4% 糖化 <mark class=\"entity\" style=\"background: #ff9561; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Drug</span></mark> 组与对照组比较无论是</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 的表达还是 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达均无统计</br>学差异(图 3、图 4)。</br>讨论</br><mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨重<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>建由<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>生成和骨吸收两部分构成,是一个动</br>态的过程。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>是骨形成、生长、发育的重要细</br>胞,其来源于<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨髓基质<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">间质细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,在<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>形成过程中经</br>历增殖、分化成熟和基质钙化三个阶段,任何一个阶段</br>出现异常都会对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>组成和骨量产生重要的影响。 目前</br>有关 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 与<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>代谢关系的研究结果存在有分歧,一些</br>研究表明 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 水平与<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨密度<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>呈负相关[6];也有研究未</br>显示两者的相关性[7]。 这可能涉及 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 的成分不一</br>和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 不同修饰,尤其是<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>高糖下极易发生 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark></br>的糖化,但糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 是否对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>代谢有影响,尤其是对</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>是否有直接影响以及如何影响未见报道。 本</br>研究发现当糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 达到 <mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">5. 3%<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark> 时,明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,且糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖的抑制作用在</br>一定程度上呈剂量及作用时间依赖性,但随着时间延</br>长,<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖化 LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 增高到一定程度则不再抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的</br>增殖。 这与氧化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的作用相似,Brodeur</br>等[8]观察到 <mark class=\"entity\" style=\"background: #7aecec; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">10 ~ 50 μg / ml<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Amount</span></mark> 的氧化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>( oxidized low</br>density lipoprotein, <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Ox-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>)可促进<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖,</br>而 150 μg / ml 浓度以上的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Ox-LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可杀死细胞并诱导</br><mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的凋亡。 Klein 等[9]发现 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 和氧化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可</br>诱导 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Saos2 成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>凋亡,同时 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 可上调促凋亡基</br>因 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Bcl-Xs<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 和下调抗凋亡 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Src 激酶<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>活性,说明 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 及其</br>修饰化在<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中具有多重功能。</br><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>在<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>矿化峰期之后才出现积聚,由<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>合成并分泌,不受<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨吸收因素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的影响,因此<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>可</br>以了解<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>特别是新形成的<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的活动状</br>态,反映了<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的活性。 临床发现<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">糖尿病<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>患者<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">血糖<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>控制不佳时<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>水平<mark class=\"entity\" style=\"background: #e4e7d2; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">明显升高<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test_Value</span></mark>[10];但机制未明。</br>本研究发现 5. 3% 糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 <mark class=\"entity\" style=\"background: #aa9cfc; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">24 h<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Duration</span></mark> 时明显抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>表达,随着 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 浓度和作用时间的增</br>加,抑制作用不断增强,而正常的糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> (糖化</br>2. 4% )与非糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 没有抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark><mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的表</br>达,说明增高糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨钙素<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>的表</br>达,提示糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 增高可能引起<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>形成的下降。</br>本研究结果显示 5. 3% 及其以上的糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在</br>24、48 和 72 h 均明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA</br>表达,显著上调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达,但正常糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 和</br>非糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达没有</br>影响,提示过度糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可通过 Wnt 信号通路 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP-5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>及其抑制剂 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达,进而影响<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的增殖</br>和分化。 而 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Wnt 通路<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>可调节<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的分化、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨基质<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>的形成及矿化、<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">破骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的功能和<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>吸收等多个环</br>节[11]。 研究显示 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可通过 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Wnt / LRP5 / β-连环蛋白<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>途径直接调节<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>功能及<mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨量<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark>[12]。 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 是</br>由细胞分泌的生物活性物质,<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可直接与 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP 受体<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>结合, 或者与其<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">跨膜受体 Kremen<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 结合后再与</br>LRP5 / 6 结合形成三聚体,诱导细胞内吞,减少细胞膜</br>上的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5 / 6<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>,从而阻断了 Wnt 信号向胞内的传递[13]。</br>此外过度表达的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK-1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 可抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨髓基质细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>向<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>分化,使<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>数量减少并抑制<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨基质<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>的矿化</br>及<mark class=\"entity\" style=\"background: #feca74; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">骨折<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Disease</span></mark>后的修复[14]。 本研究结果显示糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 在 24</br>h 时明显下调<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>中的 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达,显著上</br>调 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达,但正常糖化 <mark class=\"entity\" style=\"background: #bfe1d9; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Test</span></mark> 和非糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark></br>对 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 和 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> mRNA 表达没有影响,提示过</br>度糖化 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LDL<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 对<mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">成骨细胞<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark>增殖和分化的抑制作用可能</br>与 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">Wnt 信号通路<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">LRP5<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 及其抑制剂 <mark class=\"entity\" style=\"background: #bfeeb7; padding: 0.45em 0.6em; margin: 0 0.25em; line-height: 1; border-radius: 0.35em; box-decoration-break: clone; -webkit-box-decoration-break: clone\">DKK1<span style=\"font-size: 0.8em; font-weight: bold; line-height: 1; border-radius: 0.35em; text-transform: uppercase; vertical-align: middle; margin-left: 0.5rem\">Anatomy</span></mark> 的表达有一定关系,其机制还需进一步进行探讨。</div>"
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